Reactive oxygen species (ROS) are natural byproducts of oxygen metabolism in the cell. At physiological levels, they play a vital role in cell signaling. However, high ROS levels cause oxidative stress, which is implicated in cardiovascular diseases (CVD) such as atherosclerosis, hypertension, and restenosis after angioplasty. Despite the great amount of research conducted to identify the role of ROS in CVD, the image is still far from being complete. A common event in CVD pathophysiology is the switch of vascular smooth muscle cells (VSMCs) from a contractile to a synthetic phenotype. Interestingly, oxidative stress is a major contributor to this phenotypic switch. In this review, we focus on the effect of ROS on the hallmarks of VSMC phenotypic switch, particularly proliferation and migration. In addition, we speculate on the underlying molecular mechanisms of these cellular events. Along these lines, the impact of ROS on the expression of contractile markers of VSMCs is discussed in depth. We conclude by commenting on the efficiency of antioxidants as CVD therapies.

Visfatin/NAMPT (nicotinamide phosphoribosyltransferase) is an adipocytokine with several intriguing properties. It was first identified as pre-B-cell colony-enhancing factor but turned out to possess enzymatic functions in nicotinamide adenine dinucleotide biosynthesis, with ubiquitous expression in skeletal muscles, liver, cardiomyocytes, and brain cells. Visfatin exists in an intracellular (iNAMPT) and extracellular (eNAMPT) form. Intracellularly, visfatin/iNAMPT plays a regulatory role in NAD⁺ biosynthesis and thereby affects many NAD-dependent proteins such as sirtuins, PARPs, MARTs and CD38/157. Extracellularly, visfatin is associated with many hormone-like signaling pathways and activates some intracellular signaling cascades. Importantly, eNAMPT has been associated with several metabolic disorders including obesity and type 1 and 2 diabetes. In this review, a brief overview about visfatin is presented with special emphasis on its relevance to metabolic diseases. Visfatin/NAMPT appears to be a unique molecule with clinical significance with a prospective promising diagnostic, prognostic, and therapeutic applications in many cardiovasculo-metabolic disorders.

Ca²⁺ sensitization has been postulated to contribute to the myogenic contraction of resistance arteries evoked by elevation of transmural pressure. However, the biochemical evidence of pressure‐induced increases in phosphorylated myosin light chain phosphatase (MLCP) targeting subunit 1 (MYPT1) and/or 17 kDa protein kinase C (PKC)‐potentiated protein phosphatase 1 inhibitor protein (CPI‐17) required to sustain this view is not currently available. Here, we determined whether Ca²⁺ sensitization pathways involving Rho kinase (ROK)‐ and PKC‐dependent phosphorylation of MYPT1 and CPI‐17, respectively, contribute to the myogenic response of rat middle cerebral arteries. ROK inhibitors (Y27632, 0.03–10 μmol l⁻¹; H1152, 0.001–0.3 μmol l⁻¹) and PKC inhibitors (GF109203X, 3 μmol l⁻¹; Gö6976; 10 μmol l⁻¹) suppressed myogenic vasoconstriction between 40 and 120 mmHg. An improved, highly sensitive 3‐step Western blot method was developed for detection and quantification of MYPT1 and CPI‐17 phosphorylation. Increasing pressure from 10 to 60 or 100 mmHg significantly increased phosphorylation of MYPT1 at threonine‐855 (T855) and myosin light chain (LC₂₀). Phosphorylation of MYPT1 at threonine‐697 (T697) and CPI‐17 were not affected by pressure. Pressure‐evoked elevations in MYPT1‐T855 and LC₂₀ phosphorylation were reduced by H1152, but MYPT1‐T697 phosphorylation was unaffected. Inhibition of PKC with GF109203X did not affect MYPT1 or LC₂₀ phosphorylation at 100 mmHg. Our findings provide the first direct, biochemical evidence that a Ca²⁺ sensitization pathway involving ROK‐dependent phosphorylation of MYPT1 at T855 (but not T697) and subsequent augmentation of LC₂₀ phosphorylation contributes to myogenic control of arterial diameter in the cerebral vasculature. In contrast, suppression of the myogenic response by PKC inhibitors cannot be attributed to block of Ca²⁺ sensitization mediated by CPI‐17 or MYPT1 phosphorylation.